P63 expression in Merkel cell carcinoma: comparative immunohistochemistry invokes TAp63 as the dominant isoform involved

Abstract

The literature suggests that p63 expression in Merkel cell carcinoma (MCC) is associated with a poor prognosis. p63 immunohistochemistry marks the 2 main isoforms of this transcriptional protein: TAp63 (tumor suppressor-like properties) and ∆Np63 (oncogenic properties). Little information about the isoform of relevance in MCC exists. p40 immunohistochemistry specifically marks ∆Np63, and using comparative, semiquantitative expression of p63 and p40, we sought to clarify the issue. Our cohort of 53 cases (28 men and 25 women, median age 79 years, interquartile range 71-88) was stratified by morphology and viral status. Immunohistochemistry (p63, p40, and cytokeratin 5/6) was performed, H-scores for nuclear expression of p63 and p40 were derived (2 observers; positivity ≥ 10), and interobserver agreement was evaluated. Clinical, pathological, and outcome data were documented. The results were analyzed statistically. Mortality amounted to 57% (median follow-up 686 days, interquartile range 292-1599). Positivity for Merkel cell polyomavirus was observed in 29 (55%) of cases. Expression of p63 and p40 was present in 36 (69%) and 4 (8%) of cases, respectively. Increased age (P = .0241), negative Merkel cell polyomavirus status (P = .0185), and p63 positivity (P = .0012) were significantly associated with mortality. The latter 2 variables were highly correlated (P = .004). The interclass correlation between the 2 sets of H-scores was 0.95. Our findings support an association between p63 expression and reduced overall survival in MCC and show consistency in scoring this prognostic parameter. TAp63 is the dominant isoform of the protein involved. The paradoxical tumor suppressor-like activity of this isoform in p63-positive MCCs with reduced overall survival requires further study.